This invention relates to semi-synthetic cephalosporin antibiotic compounds. In particular, it relates to cephalosporin compounds wherein the bicyclic cephalosporin nucleus is substituted in the 3'-position with quinolinium or a substituted quinolinium group, and in the 7-position with an acetamido group substituted by a 5-membered heterocyclic ring containing one or two nitrogen atoms and an oxygen atom, and an oxime group or substituted oxime group.
Cephalosporin compounds substituted in the 3'-position with a quaternary ammonium group have been known for some time. For example, cephalosporin C.sub.A (pyridine) was one of the first derivatives of cephalosporin C prepared by Abraham et al. following the discovery of cephalosporin C, Hale, Newton, and Abraham, Biochem. J., 79, 403 (1961).
Cephaloridine, the well-known clinical antibiotic, is the 3'-pyridinium cephalosporin, 7-(.alpha.-thienylacetamido)-3-(pyridinium-1-ylmethyl)-3-cephem-4-carboxyl ate. Recently, Heymes et al., U.S. Pat. No. 4,152,432, described semi-synthetic cephalosporin antibiotics wherein the 7-position side chain is a 7-[2-(2-aminothiazol-4-yl)-2-alkoxyiminoacetamido] group and the 3'-position substituent is acetoxymethyl. More recently, O'Callaghan, et al., in U.S. Pat. No. 4,258,041, describe 7-[2-(2-aminothiazole-4-yl)-2-oximinoacetamido]-3-(pyridinium-1-ylmethyl)- 3-cephem-4-carboxylate antibiotics, and the corresponding compounds wherein the pyridinium group in the 3'-position is substituted with a carbamoyl group. These cephalosporin compounds of Heymes and O'Callahan, et al., are reported to be highly effective antibacterial agents.
Because of the continuing need for improved antibiotic therapy in clinical practice, the search continues for broader spectrum antibiotics with greater potency and minimal toxicity. The semi-synthetic cephalosporin antibiotics long have been recognized as broad spectrum antibiotics, and several have achieved clinical importance. Continued research with the cephalosporin antibiotics has centered of late on the development of antibiotics having higher activity against certain gram-negative microorganisms such as pseudomonas and those which produce .beta.-lactamase destructive of .beta.-lactam antibiotics.